1. Field of the Invention
The present invention relates to carbapenem compounds which have excellent antimicrobial activity and a broad antimicrobial spectrum. More particularly, the present invention relates to novel carbapenem derivatives having a thioethenylthiazole group at the 2-position on the carbapenem ring.
2. Background Art
Carbapenem derivatives have potent antimicrobial activity and an excellent broad antimicrobial spectrum and thus have been energetically studied as a highly useful β-lactam agent, and Imipenem, Panipenem, Meropenem, and Biapenem have already been clinically used.
A group of compounds using various linking modes at the 2-position of the carbapenem ring have been studied (Expert Opinion Therapeutic Patents, (England), 2001, 11(8), pp. 1267-1276). Among others, a group of compounds having a heterocyclic ring at the 2-position of the carbapenem ring through a sulfur atom have been studied.
Further, for example, Japanese Patent Laid-Open No. 40487/1982 discloses compounds having a hydrogen atom at the 1-position of the carbapenem ring and a thioethenyltetrazole group at the 2-position of the carbapenem ring. Japanese Patent Laid-Open No. 12675/1996 and Japanese Patent Laid-Open No. 12676/1996 disclose compounds having methyl at the 1-position on the carbapenem ring (sometimes called “1β-methyl”) and a thioalkenylenehalophenyl or thioalkenylenepyridyl group at the 2-position on the carbapenem ring. Furthermore, Japanese Patent Laid-Open No. 279888/1989 discloses compounds having methyl at the 5-position on the carbapenem ring and having a side chain through a sulfur atom at the 2-position on the carbapenem ring.
All the above publications, however, neither disclose nor suggest compounds having a thioethenylthiazole group at the 2-position of the carbapenem ring.
Japanese Patent Laid-Open No. 332288/2002 discloses cephalosporin compounds having thioethenylthiazole. This publication, however, neither discloses nor suggests antimicrobial activity against pneumococci including penicillin resistant Streptococcus pneumoniae (hereinafter often abbreviated to “PRSP”), Haemophilus influenzae including β-lactamase-negative, ampicillin-resistant Haemophilus influenzae (hereinafter often abbreviated to “BLNAR”), Moraxella (Branhamella) catarrhalis, and resistant Pseudomonas aeruginosa which currently pose clinical problems.
Further, Japanese Patent Laid-Open No. 332288/2002 describes 4-tritylthioethenylthiazole having methyl at the 4-position of the thiazole ring. However, any thiazole having other substituent is not disclosed. Further, the production process of this compound is different from that of the present invention. Furthermore, in the same publication, although 5-ethynyl-4-methylthiazole is disclosed, any thiazole having other substituent is not disclosed.
It is hard to say that the above compounds have satisfactory antimicrobial activity against methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant Enterococcus, penicillin resistant Streptococcus pneumoniae (PRSP), β-lactamase-negative, ampicillin-resistant Haemophilus influenzae (BLNAR), and resistant Pseudomonas aeruginosa which currently pose serious clinical problems. Thus, any satisfactory medicament has not been developed.
The carbapenem derivatives and cephalosporin derivatives disclosed in the above prior art documents are not always satisfactory in terms of antimicrobial activity against bacteria including various resistant bacteria. Accordingly, the development of compounds having satisfactory activity against various resistant bacteria and infectious disease causing bacteria has still been desired.